The SIRT1 Activator SRT1720 Extends Lifespan and Improves Health of Mice Fed a Standard Diet

TLDR

Preventing age‑related diseases extends survival and improves quality of life, and activation of SIRT1 improves metabolism and protects against age‑related disturbances, with the specific activator SRT1720 previously shown to benefit mice on a high‑fat diet. SRT1720 supplementation in standard‑diet mice extended lifespan, delayed the onset of age‑related metabolic diseases, improved general health, reduced proinflammatory gene expression in liver and muscle, and lowered NF‑κB phosphorylation only when SIRT1 was functional, confirming its broad health benefits across the lifespan.

Abstract

The prevention or delay of the onset of age-related diseases prolongs survival and improves quality of life while reducing the burden on the health care system. Activation of sirtuin 1 (SIRT1), an NAD(+)-dependent deacetylase, improves metabolism and confers protection against physiological and cognitive disturbances in old age. SRT1720 is a specific SIRT1 activator that has health and lifespan benefits in adult mice fed a high-fat diet. We found extension in lifespan, delayed onset of age-related metabolic diseases, and improved general health in mice fed a standard diet after SRT1720 supplementation. Inhibition of proinflammatory gene expression in both liver and muscle of SRT1720-treated animals was noted. SRT1720 lowered the phosphorylation of NF-κB pathway regulators in vitro only when SIRT1 was functionally present. Combined with our previous work, the current study further supports the beneficial effects of SRT1720 on health across the lifespan in mice.